High Aspect Ratio Nanotubes Formed by Tobacco Mosaic Virus for Delivery of Photodynamic Agents Targeting Melanoma

Lee, Karin L.; Carpenter, Bradley L.; Wen, Amy M.; Ghiladi, Reza A.; Steinmetz, Nicole F.

doi:10.1021/acsbiomaterials.6b00061

Cited by 47 publications

(55 citation statements)

References 50 publications

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“…TMV was loaded with cationic photosensitizers using the electrostatically-driven loading protocol described above (see Figure 2) [32]; the resultant PDT-carrier system showed increased cell uptake and cell killing efficiency when tested with melanoma cells in vitro [35]. CPMV modified with a corona of negatively charged dendrons was used to complex and load positively charged PDT agents.…”

Section: Drug Deliverymentioning

confidence: 99%

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

Czapar

Steinmetz

2017

Current Opinion in Chemical Biology

107

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There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals. Their protein-based structures are often understood at atomic resolution and are amenable to modification with atomic-level precision through chemical and genetic engineering. Here we present a focused review of the emerging technology development of plant viruses and bacteriophages targeting human health and agricultural applications. Key target areas of development are their use in chemotherapy-, photodynamic therapy-, pesticide-delivery, gene therapy, vaccine carriers, and immunotherapy.

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Section: Drug Deliverymentioning

confidence: 99%

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

Czapar

Steinmetz

2017

Current Opinion in Chemical Biology

107

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“…(b) MTT cell viability assay of cells after 8 h of particle uptake and white light illumination for half an hour revealed a slight increase in cell killing efficacy for particulate delivery of PS. Free PS had a IC 50 of 0.54 μ M (data reproduced from ref 21), while PS-CPMV* had an IC 50 of 0.28 μ M.…”

Section: Figurementioning

confidence: 82%

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells

Wen¹,

Lee²,

Cao³

et al. 2016

Bioconjugate Chem.

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Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.

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“…This work expands the library of plant virus-based nanoDDS approaches. In recent years, a number of drug-loaded plant virus-based formulations have been developed; for example, we demonstrated efficacy of platinum drug candidates 28 as well as photodynamic agents 36 delivered by TMV. Similarly, we and others have also shown efficacy of doxorubicin-conjugated TMV rods, disks, and spherical nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Featured Article: Delivery of chemotherapeutic vcMMAE using tobacco mosaic virus nanoparticles

Kernan

Wen

Pitek

et al. 2017

Exp Biol Med (Maywood)

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Due to side effects associated with systemic chemotherapy, there is an urgent need for the development of novel drug delivery systems. We focus on the highaspect ratio nanotubes formed by tobacco mosaic virus (TMV) to deliver antimitotic drugs targeted to non-Hodgkin's lymphoma. Many synthetic and biologic nanocarriers are in the development pipeline; the majority of systems are spherical in shape. This may not be optimal, because high-aspect ratio filaments exhibit enhanced tumor homing, increased target cell interactions and decreased immune cell uptake, and therefore have favorable properties for drug delivery compared to their spherical counterparts. Nevertheless, the synthesis of high-aspect ratio materials at the nanoscale remains challenging; therefore, we turned toward the nucleoprotein components of TMV as a biologic nanodrug delivery system. This work presents groundwork for the development of plant virus-based vehicles for use in cancer treatment. AbstractThe first-line treatment for non-Hodgkin's lymphoma is chemotherapy. While generally well tolerated, off-target effects and chemotherapy-associated complications are still of concern. To overcome the challenges associated with systemic chemotherapy, we developed a biology-inspired, nanoparticle drug delivery system (nanoDDS) making use of the nucleoprotein components of the tobacco mosaic virus (TMV). Virus-based nanoparticles, including the high-aspect ratio soft nanorods formed by TMV, are growing in popularity as nanoDDS due to their simple genetic and chemical engineerability, size and shape tunability, and biocompatibility. In this study, we used bioconjugation to modify TMV as a multivalent carrier for delivery of the antimitotic drug valine-citrulline monomethyl auristatin E (vcMMAE) targeting non-Hodgkin's lymphoma. We demonstrate successful synthesis of the TMV-vcMMAE; data indicate that the TMV-vcMMAE particles remained structurally sound with all of the 2130 identical TMV coat proteins modified to carry the therapeutic payload vcMMAE. Cell uptake using Karpas 299 cells was confirmed with TMV particles trafficking to the endolysosomal compartment, likely allowing for protease-mediated cleavage of the valine-citrulline linker for the release of the active monomethyl auristatin E component. Indeed, effective cell killing of non-Hodgkin's lymphoma in vitro was demonstrated; TMV-vcMMAE was shown to exhibit an IC 50 of $250 nM. This study contributes to the development of viral nanoDDS.

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High Aspect Ratio Nanotubes Formed by Tobacco Mosaic Virus for Delivery of Photodynamic Agents Targeting Melanoma

Cited by 47 publications

References 50 publications

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells

Featured Article: Delivery of chemotherapeutic vcMMAE using tobacco mosaic virus nanoparticles

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